Bacterial phospholipase inhibitors as modulator of colonic bacterial flora

Abstract

The present invention relates to the field of gastroenterology and, more particular, to the field of intestinal diseases. More specifically, it concerns uses and methods for the treatment of inflammatory bacterial diseases of the intestine. In particular, it relates to diseases that are associated with bacterial invasion of the intestinal mucus, including, inflammatory bowel diseases, and infectious bacterial diseases. Therefore, the present invention provides agents, a pharmaceutical composition and a kit for treating said diseases. It further relates to a use and a method for treating invasive bacterial diseases of the large intestine.

The invention claimed is: 
     
       1. A method for inhibiting bacterial phospholipase A 2  and phospholipase C in a subject, the method comprising the step of:
 (a) administering to the subject an effective amount of a pharmaceutical composition comprising a lysophospholipid-conjugate; and 
 (b) inhibiting bacterial phospholipase A 2  and phospholipase C. 
 
     
     
       2. The method according to  claim 1 , wherein the the subject has an inflammatory bacterial disease of the intestine. 
     
     
       3. The method according to  claim 2 , wherein the inflammatory bacterial disease of the intestine is invasive. 
     
     
       4. The method according to  claim 2 , wherein the intestine is the large intestine. 
     
     
       5. The method according to  claim 1 , wherein the subject is a mammal. 
     
     
       6. The method according to  claim 2 , wherein the inflammatory bacterial disease is selected from the group consisting of appendicitis, pseudoappendicits, ulcerative colitis, Crohn's disease, enterohemorrhagic colitis, pseudomembranous colitis, collagenous colitis, lymphocytte colitis, ischemic colitis, diversion colitis, microscopic colitis, Behçet's disease, indeterminate colitis, diverticulitis, megacolon, toxic megacolon, and enterocolitis. 
     
     
       7. The method according to  claim 1 , wherein the lysophospholipid-conjugate comprises a lysophospholipid chemically coupled to a bile acid. 
     
     
       8. The method according to  claim 7 , wherein the bile acid is ursodeoxycholate or deoxycholate. 
     
     
       9. The method according to  claim 1 , wherein the lysophospholipid-conjuaate comprises lysophosphatidylethanolamine or lysophosphatidylcholine. 
     
     
       10. The method according to  claim 1 , wherein the method further comprises the step of:
 (c) administering to the subject one or more agents selected from the group consisting of an antibiotic, an anti-inflammatory agent, an immunosuppressive agent, and an anti-diarrheal agent. 
 
     
     
       11. The method according to  claim 10 , wherein the one or more agents are administered prior to, simultaneously, or after step (a). 
     
     
       12. The method according to  claim 1 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
       13. The method according to  claim 10 , wherein the lysophospliolipid-conjugate and the one or more agents are administered as combination therapy.